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Racemic and chiral 3-(2, 3-butadienyl)oxoindolone compound, and preparation method and application thereof

A technology of indolinone and butadiene, which is applied in the field of transformation and antiviral application, can solve the problems that have not been studied, and achieve the effect of broad-spectrum antiviral activity

Active Publication Date: 2021-10-26
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the transition-metal-catalyzed coupling reaction between oxindolinone and 2,3-butadienol derivatives has not been studied so far.

Method used

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  • Racemic and chiral 3-(2, 3-butadienyl)oxoindolone compound, and preparation method and application thereof
  • Racemic and chiral 3-(2, 3-butadienyl)oxoindolone compound, and preparation method and application thereof
  • Racemic and chiral 3-(2, 3-butadienyl)oxoindolone compound, and preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0101]

[0102] Table 1

[0103]

[0104]

[0105] Operation steps: After the Schlenk reaction tube is dried by a heat gun, connect the argon gas cylinder to cool down to room temperature, pump and change the gas 3 times, add [Pd] (0.01mmol), 1a (0.24mmol), 2a in sequence under the protection of argon (0.2mmol), organic solvent (1.0mL), put into the preset 25 ℃ cold bath, stir for 12 hours; put the Schlenk reaction tube out of the cold bath, and use a silica gel short column (height: 3cm, diameter: 3.5cm) for the reaction solution ) filter, and rinse with 50mL of ether, concentrate, add 17.5 μL of dibromomethane, 0.8mL of deuterated chloroform, and analyze by proton nuclear magnetic spectrum, get racemic 3-(2,3-butadienyl) oxidolinone Compound 3aa NMR yield.

Embodiment 2

[0107]

[0108] After the Schlenk reaction tube was dried with a heat gun, it was connected to an argon gas cylinder and pumped to cool to room temperature, and the gas was exchanged for 3 times, and Pd(PPh 3 ) 4 (57.5mg, 0.05mmol), 1a (266.5mg, 1.2mmol), and 2a (203.8mg, 1.0mmol) / MeCN (5.0mL), the Schlenk reaction tube was placed in a preset 25 ° C oil bath, stirred for 5.5 hour (detected by thin-layer chromatography (TLC)), the Schlenk reaction tube was taken out of the oil bath and returned to room temperature, the reaction solution was filtered with a silica gel short column (height: 3cm, diameter: 3.5cm), and rinsed with 60mL of ether , concentrated, flash column chromatography [eluent: petroleum ether / ethyl acetate=15 / 1] to obtain racemic 3-(2,3-butadienyl) oxindolinone compound 3aa (246.7mg, 90%), oily liquid, 1 H NMR (400MHz, CDCl 3 )δ=7.37(d, J=7.6Hz, 2H, ArH), 7.36-7.18(m, 5H, ArH), 7.10(t, J=7.4Hz, 1H, ArH), 6.87(d, J=7.6Hz , 1H, ArH), 4.80-4.70 (quintet, J =...

Embodiment 3

[0110]

[0111] Operation is with embodiment 2. Pd(PPh 3 ) 4 (57.5mg, 0.05mmol), 1b (372.0mg, 1.2mmol), 2a (205.0mg, 1.0mmol), MeCN (5.0mL) reacted for 10.7 hours to give 3ba (318.1mg, 88%), an oily liquid, [first Sub-column chromatography, eluent: sherwood oil / ethyl acetate=30 / 1, collect all products The second column chromatography, eluent: sherwood oil / ether / dichloromethane=20 / 1 / 1] , 1 H NMR (400MHz, CDCl 3 )δ=7.94(d, J=8.0Hz, 1H, ArH), 7.40-7.15(m, 8H, ArH), 4.82-4.73(quintet, J=7.4Hz, 1H,=CH), 4.58-4.50(m ,1H, one protonof=CH), 4.50-4.40(m, 1H, one proton of=CH), 3.14-3.05(m, 1H, one proton of CH 2 ),3.00-2.88(m,1H,one proton of CH 2 ),1.61(s,9H,CH 3 ×3); 13 C NMR (100MHz, CDCl 3 )δ=210.2, 176.1, 149.3, 140.1, 139.1, 130.2, 128.61, 128.56, 127.7, 127.3, 125.2, 124.3, 115.2, 84.3, 84.1, 74.7, 56.8, 37.7, 28.1; -1):2999,2981,2930,2907,1945,1768,1724,1605,1477,1461,1418,1392,1369,1342,1284,1249,1214,1144,1101,1076,1045,1033,1000; MS( 70eV,EI)m / z(%):361[M + ,2....

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Abstract

The invention discloses a racemic and chiral 3-(2, 3-butadienyl)oxoindolone compound, a method for preparing the compound by adopting a palladium-catalyzed coupling reaction, and application of the compound. According to the method, 2, 3-butadienyl carbonate and oxoindolone react in an organic solvent in the presence of a palladium catalyst to directly construct the racemic 3-(2, 3-butadienyl)oxoindolone compound in one step. If the palladium catalyst and the chiral phosphine ligand are used in a system and react in then organic solvent, the chiral 3-(2, 3-butadienyl)oxoindolone compound can be directly constructed in one step, and the compound can be easily converted into other complex molecules. The method is convenient to operate, raw materials and reagents are easy to obtain, the substrate universality is wide, the functional group compatibility is good, and the reaction has good conversion rate and high enantioselectivity and chemical selectivity. Besides, the 3-(2, 3-butadienyl)oxoindolone compound and related derivatives thereof provided by the invention can be combined with SRAS-CoV-2 main protein 3CL hydrolase, and have a good application prospect in the aspect of treating human virus infection.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a palladium-catalyzed coupling reaction for preparing racemized and chiral 3-(2,3-butadienyl)oxindolinone compounds and their transformation and antiviral properties application. Background technique [0002] Allene compounds are widely used in organic synthesis (Ref: Ye, J.; Ma, S. Acc. Chem. Res. 2014, 47, 989), pharmaceutical research (Ref: Hoffmann- A.; Krause, N.Angew.Chem.Int.Ed.2004, 43, 1196) and in material applications (Ref: Rivera-Fuentes, P.; Diederich, F.Angew.Chem., Int.Ed.2012, 51, 2818). How to construct four-substituted optically active quaternary carbon centers simply and efficiently has been widely studied in the past ten years, and good results have been achieved. However, the reported methods are still very limited, so the development of new strategies to construct such molecules with high efficiency and high stereoselectivity has a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12C07D491/052C07F5/02A61P31/14A61K31/404
CPCC07D209/12C07D491/052C07F5/02A61P31/14C07B2200/07A61K31/404A61P31/12C07C209/66C07C225/20Y02P20/55
Inventor 麻生明林杰贾敏强程宝陈勤钱辉
Owner FUDAN UNIV
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